With the development of a qualitative method for the prediction of cycloaddition reaction rates and products, it is now possible to rationally design the synthesis of heterocyclic analogs of clinical drugs useful in cancer chemotherapy, and in the treatment of nervous disorders, hypertension, and allergies. This research project will involve the synthesis of these types of compounds, using synthetic methodology based on perturbation molecular orbital theory. Alongside the synthetic studies, molecular orbital calculations on benzodiazepines and other drug series will be carried out, both to discern the relationship between physical properties and biological activity, and to facilitate the rational design of active compounds.